The treatment of many diseases requires regular subcutaneous skin injections. For example, diabetes patients may need insulin injections following every meal and, in addition, a continuously administered low “basal” rate of insulin. The major technologies currently in use for frequent or continuous drug delivery are syringes, pre-filled pen injectors, and patient-filled portable drug pump devices. Each of these technologies has problems. For example, syringes, unless filled by a well-trained and skilled person (e.g., a health-care professional), can easily trap bubbles during the filling process, posing a risk to patient safety. Further, certain therapies require injection volumes greater than 1 ml; protein solutions, for example, often cannot be formulated with high concentration because the proteins precipitate in high concentrations, requiring large-volume injections instead. Large injection volumes, however, generally preclude the use of syringes because more than 1 ml can cause pain and swelling when injected at high rates of flow, such as with a syringe. Pre-filled pen injectors are advantageous in that they facilitate accurate manual insulin dosing using a pre-filled, bubble-free glass cartridge, which renders the priming process simple for the patient. However, since the injection is done manually, deficient patient compliance (e.g., improper injection timing and/or failure to follow the dosing prescription) is a major concern.
Portable drug pump devices can provide fully-controlled drug delivery; therefore, patient compliance is much improved. Decreased numbers of injections (once every three days, for example) and programmable dosing schedules may greatly enhance the patient's quality of life. In addition, many portable pump devices are provided in the form of patch pumps with low pump profiles, which can be attached to the patient's skin without interfering with daily activities such as showering, sleeping, and exercising. Controllable pump devices can, further, deliver drugs at slower rates than syringes and pen-injectors, thereby facilitating the injection of higher volumes of fluid (e.g., 1-10 ml) without causing discomfort or damage to local tissue; this is particularly important for viscous drug solutions (e.g., with viscosities of 35 cSt or higher). However, since these pumps are typically filled by patients, risks arise during the priming procedure. Improperly primed reservoirs may contain large air bubbles and cause the pump to inject too much air into the subcutaneous tissue, which is a serious safety matter. Moreover, many portable drug pump devices, including commercial insulin pumps, are driven by step motors (or similar components for rotating a gear). Step motors are known for their accurate rotational pitch control; however, their motion is discrete, not continuous. Therefore, the basal delivery flow provided by the step motor is also discrete. For example, basal rates in the range from 5 to 5000 nl/min—the typical dosage regime for insulin—are achieved by many systems with discrete 5 nl deliveries at rates between one delivery per hour and one thousand deliveries per hour. This discontinuous drug delivery is a major limitation of step-motor-driven insulin pumps.
Recently developed electrolytically driven piston pump devices that utilize a pre-filled glass (or polymer) vial in a pen-injection configuration solve many of the problems associated with prior technologies. They facilitate steady, continuous drug flow at a programmed rate, avoiding patient compliance issues. Additionally, the use of a pre-filled vial obviates the need for the patient to fill the drug reservoir, rendering the pump simpler to use and eliminating the risks of drug leakage due to improper filing and of introduction of particulates or foreign matter into the patient's subcutaneous tissue. However, providing controlled and accurate drug delivery still remains a challenge for pumps utilizing glass vials as drug reservoirs. This challenge arises largely from variable stiction/friction forces between the glass vial and the piston or plunger that drives the drug out of the vial. The resulting unstable flow resistance makes the drug flow difficult to control. It tends to cause basal drug delivery to suffer from varying flow rates despite constant driving pressure, and can render bolus delivery unpredictable from one bolus to the next. Accordingly, there is a need for improved flow control schemes and mechanisms to ensure constant, accurate, and predictable drug dosages for both basal and bolus deliveries.